This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Like proteins, RNA folds into well-defined three-dimensional structures required for function. The RNA folding problem aims to understand the molecular and dynamic principles of how RNA structures are built. Solving the RNA folding problem requires knowledge of the structure of folding intermediates. Our long-term goal is to determine the structures of a series of equilibrium and kinetic folding intermediates to fully delineate an entire folding pathway for different tertiary RNAs. Our short term goal is to establish the feasibility of the cryo-EM technique for structure studies of native and folding intermediates of RNAs weighing less than 100 kD.